We have shown that age accounts for a significant fraction of testicular variation in normal men, but much of the variation in the quantitative characteristics of human testes remains to be explained. The proposed research will seek explanatory correlates of the variation in numbers of Leydig and Sertoli cells and in daily sperm production that occurs within groups of old or young men. Specific hypotheses to be tested include the possibility that over-nutrition (obesity), alcoholism, or drug-abuse may accelerate age-related testicular changes or account for some of the variation in "normal" human testes. The work will also determine the subcellular composition of the Leydig cell population to discern its relationships to rates of sperm production, and it will examine the hypothesis that the cytological features of human Leydig cells vary according to the spermatogenic activity of adjacent seminiferous tubules. The proposed research will also identify where in early spermatogenesis old men initially experience the disproportionate reduction in germ cells leading to lower daily sperm production in comparison to young men. Testicular characteristics to be measured include: numbers of Leydig cells, average volume of a single Leydig cell, numbers of Sertoli cells, daily sperm production, potential daily sperm production based both on spermatocytes and spermatogonia, average diameter of the seminiferous tubules, total length of the seminiferous tubules, average thickness of tubular boundary tissue, total luminal volume of the blood vascular system, surface density of the blood vascular system, and average thickness of the capillary endothelium and basement membrane. Testes used in this study will be obtained at autopsy from normal men, dead of heart attack or trauma, between 20 and 80 years of age. This research will help fill the need for better understanding of the factors that influence androgen status and sperm production in men.